1. Field of the Invention
The present invention relates to a process of preparing a stable prostaglandin E group-containing formulation and more particularly it relates to a process of preparing a prostaglandin E group-containing formulation by adding to a prostaglandin group E at least one additive selected from the group consisting of a thiol compound, a water-soluble high molecular weight compound and a water-soluble salt of deoxycholic acid and subjecting the mixture to lyophilization.
In the invention, the term "prostaglandin E group" means prostaglandin E.sub.1 represented by the formula ##STR1## prostaglandin E.sub.2 represented by the formula ##STR2## prostaglandin E.sub.3 represented by the formula ##STR3## and the derivatives of these compound at the side chains, such as, for example, 16-methyl-prostaglandin E.sub.2, 3-methyl-prostaglandin E.sub.2, 3,16(R)-dimethyl-prostaglandin E.sub.2, 17-oxo-15-epi-prostaglandin E.sub.2, 16(R)-hydroxy-prostaglandin E.sub.2, etc.
2. Description of the Prior Art
Prostaglandin E group is a medicament showing, even in a small amount, such medical actions as the control of the contractive force of the uterus, a hypotensive effect, treatment and prophylaxis of digestive organ ulcers, control of lipid metabolism, bronchodilator action, etc. However, since the compound is very unstable and is liable to be decomposed; that is, the compound is easily decomposed in not only a solution state but also in a crystalline state, it is ordinarily stored as the crystal thereof or an ethanol solution thereof in a refrigerator at -20.degree. C.
For stabilizing the prostaglandin E group, a process has hitherto been known in which the compound is dissolved in an organic solvent such as N,N-dimethylacetamide containing less than 0.1% water as disclosed in Belgian Pat. No. 790,840.
However, in the case of administering a medicament directly to the human body, in particular, administering by injection, the medicament may sometimes be administered in the form of an organic solution or in the form of an organic solution diluted with water but it is usually preferred to adminnister the medicament in the form of an aqueous solution (see, e.g., "Dispensing of Medication", 976(1971), 7th Ed., Mack Publishing Company).
Consequently, a stable prostaglandin E group-containing formulation is one which can store prostaglandin E group in a stable form and can be administered as an aqueous solution when administering by injection is desirable.